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An acquired phosphatidylinositol 4-phosphate transport initiates T-cell deterioration and leukemogenesis

Author

Listed:
  • Wenbin Zhong

    (Jinan University
    Affiliated Cancer Hospital and Institute of Guangzhou Medical University)

  • Weize Lin

    (Jinan University)

  • Yingjie Yang

    (Jinan University)

  • Dan Chen

    (Jinan University)

  • Xiuye Cao

    (Jinan University)

  • Mengyang Xu

    (Jinan University
    Sun Yat-Sen University)

  • Guoping Pan

    (Jinan University)

  • Huanzhao Chen

    (Jinan University)

  • Jie Zheng

    (Jinan University)

  • Xiaoqin Feng

    (Southern Medical University)

  • Li hua Yang

    (Southern Medical University)

  • Chaofeng Lai

    (Jinan University)

  • Vesa M. Olkkonen

    (Minerva Foundation Institute for Medical Research, Biomedicum 2U
    University of Helsinki)

  • Jun Xu

    (Sun Yat-Sen University)

  • Shuzhong Cui

    (Affiliated Cancer Hospital and Institute of Guangzhou Medical University)

  • Daoguang Yan

    (Jinan University
    Affiliated Cancer Hospital and Institute of Guangzhou Medical University)

Abstract

Lipid remodeling is crucial for malignant cell transformation and tumorigenesis, but the precise molecular processes involved and direct evidences for these in vivo remain elusive. Here, we report that oxysterol-binding protein (OSBP)-related protein 4 L (ORP4L) is expressed in adult T-cell leukemia (ATL) cells but not normal T-cells. In ORP4L knock-in T-cells, ORP4L dimerizes with OSBP to control the shuttling of OSBP between the Golgi apparatus and the plasma membrane (PM) as an exchanger of phosphatidylinositol 4-phosphate [PI(4)P]/cholesterol. The PI(4)P arriving at the PM via this transport machinery replenishes phosphatidylinositol 4,5-bisphosphate [PI(4,5)P2] and phosphatidylinositol (3,4,5) trisphosphate [PI(3,4,5)P3] biosynthesis, thus contributing to PI3K/AKT hyperactivation and T-cell deterioration in vitro and in vivo. Disruption of ORP4L and OSBP dimerization disables PI(4)P transport and T-cell leukemogenesis. In summary, we identify a non-vesicular lipid transport machinery between Golgi and PM maintaining the oncogenic signaling competence initiating T-cell deterioration and leukemogenesis.

Suggested Citation

  • Wenbin Zhong & Weize Lin & Yingjie Yang & Dan Chen & Xiuye Cao & Mengyang Xu & Guoping Pan & Huanzhao Chen & Jie Zheng & Xiaoqin Feng & Li hua Yang & Chaofeng Lai & Vesa M. Olkkonen & Jun Xu & Shuzhon, 2022. "An acquired phosphatidylinositol 4-phosphate transport initiates T-cell deterioration and leukemogenesis," Nature Communications, Nature, vol. 13(1), pages 1-18, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-32104-7
    DOI: 10.1038/s41467-022-32104-7
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    References listed on IDEAS

    as
    1. Wenbin Zhong & Qing Yi & Bing Xu & Shiqian Li & Tong Wang & Fupei Liu & Biying Zhu & Peter R. Hoffmann & Guangju Ji & Pingsheng Lei & Guoping Li & Jiwei Li & Jian Li & Vesa M. Olkkonen & Daoguang Yan, 2016. "ORP4L is essential for T-cell acute lymphoblastic leukemia cell survival," Nature Communications, Nature, vol. 7(1), pages 1-14, November.
    2. Eugenio Mora & Manuela Dezi & Aurélie Cicco & Joëlle Bigay & Romain Gautier & John Manzi & Joël Polidori & Daniel Castaño-Díez & Bruno Mesmin & Bruno Antonny & Daniel Lévy, 2021. "Nanoscale architecture of a VAP-A-OSBP tethering complex at membrane contact sites," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
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